Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogen...

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Autores principales:	Mas Rizky A A Syamsunarno, Tatsuya Iso, Aiko Yamaguchi, Hirofumi Hanaoka, Mirasari Putri, Masaru Obokata, Hiroaki Sunaga, Norimichi Koitabashi, Hiroki Matsui, Kazuhisa Maeda, Keigo Endo, Yoshito Tsushima, Tomoyuki Yokoyama, Masahiko Kurabayashi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/583669a39c824374b6570c6da0b67f53
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spelling	oai:doaj.org-article:583669a39c824374b6570c6da0b67f532021-11-18T08:29:23ZFatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.1932-620310.1371/journal.pone.0090825https://doaj.org/article/583669a39c824374b6570c6da0b67f532014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603714/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.Mas Rizky A A SyamsunarnoTatsuya IsoAiko YamaguchiHirofumi HanaokaMirasari PutriMasaru ObokataHiroaki SunagaNorimichi KoitabashiHiroki MatsuiKazuhisa MaedaKeigo EndoYoshito TsushimaTomoyuki YokoyamaMasahiko KurabayashiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e90825 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mas Rizky A A Syamsunarno Tatsuya Iso Aiko Yamaguchi Hirofumi Hanaoka Mirasari Putri Masaru Obokata Hiroaki Sunaga Norimichi Koitabashi Hiroki Matsui Kazuhisa Maeda Keigo Endo Yoshito Tsushima Tomoyuki Yokoyama Masahiko Kurabayashi Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
description	Hypothermia is rapidly induced during cold exposure when thermoregulatory mechanisms, including fatty acid (FA) utilization, are disturbed. FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipose tissues and macrophages, have been identified as key molecules in the pathogenesis of overnutrition-related diseases, such as insulin resistance and atherosclerosis. We have recently shown that FABP4/5 are prominently expressed in capillary endothelial cells in the heart and skeletal muscle and play a crucial role in FA utilization in these tissues. However, the role of FABP4/5 in thermogenesis remains to be determined. In this study, we showed that thermogenesis is severely impaired in mice lacking both FABP4 and FABP5 (DKO mice), as manifested shortly after cold exposure during fasting. In DKO mice, the storage of both triacylglycerol in brown adipose tissue (BAT) and glycogen in skeletal muscle (SkM) was nearly depleted after fasting, and a biodistribution analysis using 125I-BMIPP revealed that non-esterified FAs (NEFAs) are not efficiently taken up by BAT despite the robustly elevated levels of serum NEFAs. In addition to the severe hypoglycemia observed in DKO mice during fasting, cold exposure did not induce the uptake of glucose analogue 18F-FDG by BAT. These findings strongly suggest that DKO mice exhibit pronounced hypothermia after fasting due to the depletion of energy storage in BAT and SkM and the reduced supply of energy substrates to these tissues. In conclusion, FABP4/5 play an indispensable role in thermogenesis in BAT and SkM. Our study underscores the importance of FABP4/5 for overcoming life-threatening environments, such as cold and starvation.
format	article
author	Mas Rizky A A Syamsunarno Tatsuya Iso Aiko Yamaguchi Hirofumi Hanaoka Mirasari Putri Masaru Obokata Hiroaki Sunaga Norimichi Koitabashi Hiroki Matsui Kazuhisa Maeda Keigo Endo Yoshito Tsushima Tomoyuki Yokoyama Masahiko Kurabayashi
author_facet	Mas Rizky A A Syamsunarno Tatsuya Iso Aiko Yamaguchi Hirofumi Hanaoka Mirasari Putri Masaru Obokata Hiroaki Sunaga Norimichi Koitabashi Hiroki Matsui Kazuhisa Maeda Keigo Endo Yoshito Tsushima Tomoyuki Yokoyama Masahiko Kurabayashi
author_sort	Mas Rizky A A Syamsunarno
title	Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_short	Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_full	Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_fullStr	Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_full_unstemmed	Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
title_sort	fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/583669a39c824374b6570c6da0b67f53
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Fatty acid binding protein 4 and 5 play a crucial role in thermogenesis under the conditions of fasting and cold stress.

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